chr20-56386354-C-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_198437.3(AURKA):ā€‹c.222G>Cā€‹(p.Gln74His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,614,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 33)
Exomes š‘“: 0.000012 ( 0 hom. )

Consequence

AURKA
NM_198437.3 missense

Scores

18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.108
Variant links:
Genes affected
AURKA (HGNC:11393): (aurora kinase A) The protein encoded by this gene is a cell cycle-regulated kinase that appears to be involved in microtubule formation and/or stabilization at the spindle pole during chromosome segregation. The encoded protein is found at the centrosome in interphase cells and at the spindle poles in mitosis. This gene may play a role in tumor development and progression. A processed pseudogene of this gene has been found on chromosome 1, and an unprocessed pseudogene has been found on chromosome 10. Multiple transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.051991373).
BS2
High AC in GnomAdExome4 at 17 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
AURKANM_198437.3 linkuse as main transcriptc.222G>C p.Gln74His missense_variant 3/9 ENST00000395915.8 NP_940839.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
AURKAENST00000395915.8 linkuse as main transcriptc.222G>C p.Gln74His missense_variant 3/91 NM_198437.3 ENSP00000379251 P1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152184
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000159
AC:
4
AN:
251486
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135918
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000352
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000116
AC:
17
AN:
1461894
Hom.:
0
Cov.:
30
AF XY:
0.00000825
AC XY:
6
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000153
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152184
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74346
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000434
Hom.:
0
Bravo
AF:
0.0000151
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsFeb 16, 2023The c.222G>C (p.Q74H) alteration is located in exon 5 (coding exon 2) of the AURKA gene. This alteration results from a G to C substitution at nucleotide position 222, causing the glutamine (Q) at amino acid position 74 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.081
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.37
CADD
Benign
10
DANN
Benign
0.62
DEOGEN2
Benign
0.013
.;.;.;.;.;.;.;.;T;.;T;T;.
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.42
N
LIST_S2
Benign
0.56
.;.;.;.;.;.;.;T;T;T;T;T;T
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.052
T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
1.0
N;N;N;N;N;N;N;N;N
PrimateAI
Benign
0.26
T
PROVEAN
Benign
-0.57
N;N;N;N;N;N;N;N;N;N;N;D;N
REVEL
Benign
0.11
Sift
Benign
0.20
T;T;T;T;T;T;T;T;T;T;T;T;T
Sift4G
Benign
0.13
T;T;T;T;T;T;T;T;.;.;.;.;.
Polyphen
0.0010, 0.0
.;.;.;.;.;.;.;B;B;B;B;B;.
Vest4
0.14
MutPred
0.11
Loss of methylation at K77 (P = 0.0998);Loss of methylation at K77 (P = 0.0998);Loss of methylation at K77 (P = 0.0998);Loss of methylation at K77 (P = 0.0998);Loss of methylation at K77 (P = 0.0998);Loss of methylation at K77 (P = 0.0998);Loss of methylation at K77 (P = 0.0998);Loss of methylation at K77 (P = 0.0998);Loss of methylation at K77 (P = 0.0998);Loss of methylation at K77 (P = 0.0998);Loss of methylation at K77 (P = 0.0998);Loss of methylation at K77 (P = 0.0998);Loss of methylation at K77 (P = 0.0998);
MVP
0.48
ClinPred
0.019
T
GERP RS
-3.7
gMVP
0.30

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs769911074; hg19: chr20-54961410; API